May 2017

Cover articles

    1. Cancer Biology
    2. Cell Biology

    A new twist in the Hippo-YAP pathway

    Susana Moleirinho, Sany Hoxha ... Joseph L Kissil
    1. Developmental Biology

    Brain lymphatics in the zebrafish embryo

    Max van Lessen, Shannon Shibata-Germanos ... Stefan Schulte-Merker
    1. Developmental Biology
    2. Neuroscience

    Differential tagging of wild-type and mutant cells

    Sonal Nagarkar-Jaiswal, Sathiya N Manivannan ... Hugo J Bellen
    1. Cell Biology
    2. Developmental Biology

    Control of geometric order in retinal cells

    Eunice HoYee Chan, Pruthvi Chavadimane Shivakumar ... Pierre-François Lenne

Highlights controls:

Research articles

    1. Cell Biology
    2. Stem Cells and Regenerative Medicine

    Oxidative stress induces stem cell proliferation via TRPA1/RyR-mediated Ca2+ signaling in the Drosophila midgut

    Chiwei Xu, Junjie Luo ... Norbert Perrimon
    In response to tissue damage, reactive oxygen species can be sensed by cation channels TRPA1/RyR to cause increases of cytosolic Ca2+ in intestinal stem cells, activating Ras/MAPK activity and stimulating stem cell proliferation in Drosophila.
    1. Cancer Biology

    Synergistic interactions with PI3K inhibition that induce apoptosis

    Yaara Zwang, Oliver Jonas ... William C Hahn
    A geneome-scale shRNA screen identifies five genes whose suppression promotes cell death upon PI3K inhibition both in vitro and in vivo, thus suggesting potential combination therapies involving PI3K inhibition.
    1. Structural Biology and Molecular Biophysics

    Structural basis for anion conduction in the calcium-activated chloride channel TMEM16A

    Cristina Paulino, Yvonne Neldner ... Raimund Dutzler
    Single-particle cryo-EM and electrophysiology studies of the chloride channel TMEM16A reveals the structural basis for anion conduction and uncover its relationship to lipid scramblases of the same family.
    1. Neuroscience

    Learning shapes the aversion and reward responses of lateral habenula neurons

    Daqing Wang, Yi Li ... Minmin Luo
    Neurons in the lateral habenula are activated by pain, bitterness and social defeat, and their responses are dynamically shaped by learning, suggesting a role in experience-dependent selection of behavioral actions to stressors.
    1. Cell Biology

    IFT trains in different stages of assembly queue at the ciliary base for consecutive release into the cilium

    Jenna L Wingfield, Ilaria Mengoni ... Karl Lechtreck
    Multimegadalton intraflagellar transport (IFT) trains assemble by sequential recruitment of IFT subcomplexes from the cell body to the ciliary basal bodies and tubulin, the main IFT cargo, is loaded briefly before trains depart.
    1. Developmental Biology
    2. Neuroscience

    A cell cycle-independent, conditional gene inactivation strategy for differentially tagging wild-type and mutant cells

    Sonal Nagarkar-Jaiswal, Sathiya N Manivannan ... Hugo J Bellen
    A conditional gene inactivation system that permits the tracking of protein expression, and creates fluorescently-labelled mutant cells in both developing and adult Drosophila tissues.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    The force-sensing peptide VemP employs extreme compaction and secondary structure formation to induce ribosomal stalling

    Ting Su, Jingdong Cheng ... Roland Beckmann
    The structure of the VemP-stalled ribosome reveals a helix-double turn-helix conformation of the nascent chain within the ribosomal tunnel, illustrating how secondary structure formation directly at the peptidyltransferase center of the ribosome can induce translational arrest.
    1. Cell Biology

    HIF-1α is required for disturbed flow-induced metabolic reprogramming in human and porcine vascular endothelium

    David Wu, Ru-Ting Huang ... Gökhan M Mutlu
    Hemodynamic forces regulate endothelial cell metabolism, which in turn regulates endothelial inflammation.
    1. Neuroscience

    Threat of shock increases excitability and connectivity of the intraparietal sulcus

    Nicholas L Balderston, Elizabeth Hale ... Christian Grillon
    Multimodal neuroimaging was used to study the effect of threat on spontaneous brain activity and functional connectivity, and demonstrated that threat increases both activity and connectivity of the intraparietal sulcus, a key node in the frontoparietal attention network.
    1. Neuroscience

    Activation of the same mGluR5 receptors in the amygdala causes divergent effects on specific versus indiscriminate fear

    Mohammed Mostafizur Rahman, Sonal Kedia ... Sumantra Chattarji
    Activation of the same glutamate receptor in the lateral amygdala gives rise to distinct effects on specific versus indiscriminate fear by modulating intrinsic excitability and synaptic plasticity.
    1. Chromosomes and Gene Expression

    Cooperation between a hierarchical set of recruitment sites targets the X chromosome for dosage compensation

    Sarah Elizabeth Albritton, Anna-Lena Kranz ... Sevinc Ercan
    Gene regulatory elements can target a chromatin regulatory complex to a single chromosome in the genome through hierarchical specification and long distance cooperation.
    1. Cell Biology
    2. Developmental Biology

    Control of PNG kinase, a key regulator of mRNA translation, is coupled to meiosis completion at egg activation

    Masatoshi Hara, Boryana Petrova, Terry L Orr-Weaver
    The kinase that controls maternal mRNA translation is regulated by phosphorylation of its activating subunit to restrict kinase activity to the developmental window between meiosis completion and early embryogenesis.
    1. Developmental Biology

    Erythropoietin signaling regulates heme biosynthesis

    Jacky Chung, Johannes G Wittig ... Barry H Paw
    EPO/JAK2/PKA signaling cascade via AKAP10 relocalization to the outer mitochondrial membrane results in the phosphorylation of the terminal heme synthesis enzyme ferrochelatase, which contributes to heme production in red cells.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    Methylated cis-regulatory elements mediate KLF4-dependent gene transactivation and cell migration

    Jun Wan, Yijing Su ... Shuli Xia
    A new paradigm of DNA methylation mediated gene activation and chromatin remodeling provides a general framework to dissect the biological functions of DNA methylation readers and effectors.
    1. Neuroscience

    Rai1 frees mice from the repression of active wake behaviors by light

    Shanaz Diessler, Corinne Kostic ... Paul Franken
    Halving dosage of the Smith-Magenis syndrome responsible gene Rai1 in the mouse greatly amplifies the direct, suppressing effects of light on active-wake behavior through increased activation of the ventral-subparaventricular zone.
    1. Microbiology and Infectious Disease

    Efficacy of β-lactam/β-lactamase inhibitor combination is linked to WhiB4-mediated changes in redox physiology of Mycobacterium tuberculosis

    Saurabh Mishra, Prashant Shukla ... Amit Singh
    Intrinsic tolerance of Mycobacterium tuberculosis toward the world's most successful antibacterials, β-lactams, is dependent on cytoplasmic redox potential and an intracellular redox-sensor WhiB4.
    1. Structural Biology and Molecular Biophysics

    Asymmetric recognition of HIV-1 Envelope trimer by V1V2 loop-targeting antibodies

    Haoqing Wang, Harry B Gristick ... Pamela J Bjorkman
    Single particle cryoEM structure of antibody complex with HIV-1 envelope trimer reveals new mode of asymmetric recognition of trimer apex.
    1. Cell Biology

    The step-wise pathway of septin hetero-octamer assembly in budding yeast

    Andrew Weems, Michael McMurray
    In budding yeast cells, slow monomeric septin GTPase activity and the cytosolic GTP:GDP ratio dictate the relative incorporation of alternative subunits during septin hetero-oligomer assembly, which proceeds by discrete, ordered steps dependent on allostery between interaction interfaces.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    Chemotactic network responses to live bacteria show independence of phagocytosis from chemoreceptor sensing

    Netra Pal Meena, Alan R Kimmel
    Eukaryotic chemotaxis to live bacteria was quantified at a high throughput level, for the first time, and mechanistically examined for the interrelationship between chemotaxis and phagocytosis.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Pausing guides RNA folding to populate transiently stable RNA structures for riboswitch-based transcription regulation

    Hannah Steinert, Florian Sochor ... Harald Schwalbe
    The discontinuous speed of transcription enables riboswitch molecules to adopt meta-stable structures in response to the presence of their cognate ligand, thereby gene-regulation by means of structure induced transcription termination can occur.
    1. Neuroscience

    Distinct responses of Purkinje neurons and roles of simple spikes during associative motor learning in larval zebrafish

    Thomas C Harmon, Uri Magaram ... Indira M Raman
    Discrete classes of cerebellar Purkinje neurons show distinct changes in synaptic and spiking activity during motor learning, with simple spikes playing a shifting role during acquisition, expression, and maintenance of learned responses.
    1. Neuroscience

    Rapid short-term reorganization in the language network

    Gesa Hartwigsen, Danilo Bzdok ... Dorothee Saur
    The beneficial contribution of a language network for a specific function depends on the level of functional disruption and may reflect the differential compensatory potential of distinct language networks.
    1. Developmental Biology
    2. Chromosomes and Gene Expression

    Enforcement of developmental lineage specificity by transcription factor Oct1

    Zuolian Shen, Jinsuk Kang ... Dean Tantin
    Oct1 replaces Oct4 at critical targets shortly after ESC differentiation to promote expression of lineage-specific genes and repress lineage-inappropriate genes.
    1. Developmental Biology
    2. Neuroscience

    Pioneer neurog1 expressing cells ingress into the otic epithelium and instruct neuronal specification

    Esteban Hoijman, L Fargas ... Berta Alsina
    Quantitative 4D image analysis identifies a group of cells which enter into the otic primordium during morphogenesis and instructs neuronal specification.
    1. Chromosomes and Gene Expression
    2. Neuroscience

    Longitudinal imaging of Caenorhabditis elegans in a microfabricated device reveals variation in behavioral decline during aging

    Matthew A Churgin, Sang-Kyu Jung ... Christopher Fang-Yen
    The WorMotel, a novel microfabricated device for automated longitudinal imaging of aging in large numbers of Caenorhabditis elegans, reveals that long and short lived strains vary in their behavioral decline during aging in a similar way to the long and short lived individuals in a wild type population.
    1. Structural Biology and Molecular Biophysics

    Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex

    Guijun Shang, Chad A Brautigam ... Xuewu Zhang
    PlexinD1 binding releases GIPC autoinhibition, leading to formation of high-order oligomers of the GIPC/myosin VI complex.
    1. Neuroscience

    Identification of a novel spinal nociceptive-motor gate control for Aδ pain stimuli in rats

    Dvir Blivis, Gal Haspel ... Michael J Iadarola
    A novel mechanism for gating nociceptive sensory-motor behavior is identified in freely behaving rats using high-speed videography that is controlled by posture and modulated by opioid and non-opioid receptor-dependent processes.
    1. Computational and Systems Biology
    2. Chromosomes and Gene Expression

    RNA-dependent chromatin association of transcription elongation factors and Pol II CTD kinases

    Sofia Battaglia, Michael Lidschreiber ... Patrick Cramer
    In vivo and in vitro elongation factor-RNA interaction data provide a missing link in understanding how processive elongation complexes are formed on active genes and disassembled at the end of genes.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    The dynamic three-dimensional organization of the diploid yeast genome

    Seungsoo Kim, Ivan Liachko ... Maitreya J Dunham
    Yeast homologous chromosomes exhibit condition-specific mitotic pairing at both global and local scales.
    1. Cell Biology
    2. Developmental Biology

    Patterned cortical tension mediated by N-cadherin controls cell geometric order in the Drosophila eye

    Eunice HoYee Chan, Pruthvi Chavadimane Shivakumar ... Pierre-François Lenne
    N-cadherin at heterotypic contacts controls the level and asymmetric localisation of Myosin-II motor, thereby influencing cell shapes and cell packing.
    1. Genetics and Genomics
    2. Microbiology and Infectious Disease

    APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis

    Anneli Cooper, Hamidou Ilboudo ... Annette MacLeod
    Common kidney disease risk variants in African populations are associated with reduced susceptibility to deadly African trypanosomes.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    Srs2 promotes synthesis-dependent strand annealing by disrupting DNA polymerase δ-extending D-loops

    Jie Liu, Christopher Ede ... Wolf-Dietrich Heyer
    The Srs2 helicase functions in Synthesis-Dependent Strand Annealing to avoid crossover formation during homologous recombination by disrupting D-loops that are extended by DNA polymerase delta in an ATP-dependent and direction-specific manner.
    1. Neuroscience

    Calcium dynamics regulating the timing of decision-making in C. elegans

    Yuki Tanimoto, Akiko Yamazoe-Umemoto ... Koutarou D Kimura
    A series of quantitative behavioural and opto-physiological analyses using a novel robot microscope system reveals that C. elegans computes the time-differential and time-integral of sensory information for decision-making during olfactory navigation.
    1. Neuroscience

    mTORC1 in AGRP neurons integrates exteroceptive and interoceptive food-related cues in the modulation of adaptive energy expenditure in mice

    Luke K Burke, Tamana Darwish ... Clémence Blouet
    AGRP neurons integrate environmental food-related cues with internal metabolic signals to modulate interscapular brown adipose tissue thermogenesis and energy expenditure, at least in part, via mTORC1 signalling.
    1. Neuroscience

    Integration of Tmc1/2 into the mechanotransduction complex in zebrafish hair cells is regulated by Transmembrane O-methyltransferase (Tomt)

    Timothy Erickson, Clive P Morgan ... Teresa Nicolson
    A zebrafish model for a particular form of human deafness (DFNB63) changes our view of this disease by revealing a defect in the localization of Transmembrane channel-like proteins that are essential for mechanotransduction in sensory cells.
    1. Neuroscience

    Optocontrol of glutamate receptor activity by single side-chain photoisomerization

    Viktoria Klippenstein, Christian Hoppmann ... Pierre Paoletti
    Introduction of single photoswitchable unnatural amino acid into a neuronal receptor provides reversible, rapid and robust control of its activity by light, representing an important contribution to the fast expanding field of optopharmacology.
    1. Neuroscience

    Wiring variations that enable and constrain neural computation in a sensory microcircuit

    William F Tobin, Rachel I Wilson, Wei-Chung Allen Lee
    Systematic and coordinated variations in morphology and connectivity can structurally tune a microcircuit's computation but non-systematic variably also exists, imparting "connection noise" that potentially limits processing performance.
    1. Neuroscience

    Angular velocity integration in a fly heading circuit

    Daniel Turner-Evans, Stephanie Wegener ... Vivek Jayaraman
    A distinctive recurrent network motif in the Drosophila central brain enables neurons that encode angular velocity to shift population activity in compass neurons, thereby updating their heading representation whenever the fly turns.
    1. Neuroscience

    A genetic basis for molecular asymmetry at vertebrate electrical synapses

    Adam C Miller, Alex C Whitebirch ... Cecilia B Moens
    Electrical synapses are neuronal, gap-junction-based connections found throughout the nervous system that, in the escape circuit of zebrafish, are composed of molecularly distinct pre- and postsynaptic junction forming proteins that are required for behavioral performance.
    1. Immunology and Inflammation

    The structure of a LAIR1-containing human antibody reveals a novel mechanism of antigen recognition

    Fu-Lien Hsieh, Matthew K Higgins
    The structure of a human antibody in which the variable loops position a human protein LAIR1 for antigen recognition, reveals a novel and indirect mode of antibody function.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    A widespread family of serine/threonine protein phosphatases shares a common regulatory switch with proteasomal proteases

    Niels Bradshaw, Vladimir M Levdikov ... Richard Losick
    Structures of active and inactive conformations of a PP2C family phosphatase reveal a conserved switch that controls enzymatic activity and point to an unexpected relationship between phosphatases and proteasomal proteases.
    1. Neuroscience

    The N-terminus of the prion protein is a toxic effector regulated by the C-terminus

    Bei Wu, Alex J McDonald ... David A Harris
    A novel auto-inhibitory mechanism regulates the functional activity of the cellular prion protein, PrPC, providing for the first time a coherent molecular model for both its pathological and physiological effects.
    1. Neuroscience

    Functional dissociation of stimulus intensity encoding and predictive coding of pain in the insula

    Stephan Geuter, Sabrina Boll ... Christian Büchel
    Pain processing in certain brain regions implements predictive coding principles, offering a novel perspective on the neural basis of pain perception.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    Malaria parasite LIMP protein regulates sporozoite gliding motility and infectivity in mosquito and mammalian hosts

    Jorge M Santos, Saskia Egarter ... Gunnar R Mair
    A small surface protein regulates gliding motility and host cell invasion by the sporozoite stage of the malaria parasite.
    1. Neuroscience

    Chronic pain induces generalized enhancement of aversion

    Qiaosheng Zhang, Toby Manders ... Jing Wang
    Chronic pain distorts intensity coding in the anterior cingulate cortex to give rise to generalized anatomically nonspecific enhancement in pain aversion.
    1. Biochemistry and Chemical Biology

    Chemical structure-guided design of dynapyrazoles, cell-permeable dynein inhibitors with a unique mode of action

    Jonathan B Steinman, Cristina C Santarossa ... Tarun M Kapoor
    Analyses of the chemical structure of ciliobrevins led to dynein inhibitors with improved properties and higher potency.
    1. Cell Biology
    2. Plant Biology

    ER assembly of SNARE complexes mediating formation of partitioning membrane in Arabidopsis cytokinesis

    Matthias Karnahl, Misoon Park ... Gerd Jürgens
    SNARE proteins are delivered as complexes already from the endoplasmic reticulum along the secretory pathway to the cell division plane to mediate the formation of the partitioning membrane by vesicle fusion.
    1. Structural Biology and Molecular Biophysics
    2. Immunology and Inflammation

    Fluorescence Lifetime Imaging Microscopy reveals rerouting of SNARE trafficking driving dendritic cell activation

    Daniëlle Rianne José Verboogen, Natalia González Mancha ... Geert van den Bogaart
    A novel microscopy-based assay shows that dendritic cells encountering pathogenic stimuli form increased complexes of specific SNARE proteins, driving release of large amounts of inflammatory cytokines.
    1. Genetics and Genomics

    On the mechanistic nature of epistasis in a canonical cis-regulatory element

    Mato Lagator, Tiago Paixão ... Călin C Guet
    Thermodynamic framework accurately predicts the sign of epistasis and its environment dependence for a canonical cis-regulatory element.
    1. Neuroscience

    A positive feedback loop linking enhanced mGluR function and basal calcium in spinocerebellar ataxia type 2

    Pratap Meera, Stefan Pulst, Thomas Otis
    A damaging form of positive feedback linking elevated calcium levels and metabotropic glutamate receptor function in Purkinje neurons plays a critical role in the pathology in spinocerebellar ataxias.
    1. Immunology and Inflammation

    Functionally diverse human T cells recognize non-microbial antigens presented by MR1

    Marco Lepore, Artem Kalinichenko ... Gennaro De Libero
    MR1T cells are human polyclonal T cells endowed with diverse effector functions in response to endogenous antigens presented by MHC-class 1-related molecule, MR1.
    1. Cell Biology

    A bioactive peptide amidating enzyme is required for ciliogenesis

    Dhivya Kumar, Daniela Strenkert ... Betty A Eipper
    Analysis of Chlamydomonas, planaria and mice reveals a novel and unanticipated role for a peptide amidating enzyme in primary and motile ciliary assembly through effects on post-Golgi trafficking.
    1. Computational and Systems Biology

    Distributing tasks via multiple input pathways increases cellular survival in stress

    Alejandro A Granados, Matthew M Crane ... Peter S Swain
    Single-cell experiments and mathematical modelling show that cellular signalling networks are vulnerable to trade-offs in speed versus accuracy, but that these vulnerabilities can be overcome by distributing the two tasks to different, although interacting, subnetworks.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Dissection of zebrafish shha function using site-specific targeting with a Cre-dependent genetic switch

    Kotaro Sugimoto, Subhra P Hui ... Kazu Kikuchi
    A versatile invertible gene trap vector is generated and inserted into a defined genomic locus in zebrafish via homologous recombination, demonstrating an efficient genetic approach to performing conditional knockout analysis.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    A unifying mechanism for the biogenesis of membrane proteins co-operatively integrated by the Sec and Tat pathways

    Fiona J Tooke, Marion Babot ... Tracy Palmer
    Bioinformatics and experimental approaches identify families of membrane proteins requiring the co-ordinated action of the Sec pathway and Tat pathways for their integration and define features of the polypeptides that mediate interaction with these pathways.
    1. Neuroscience

    Ciliomotor circuitry underlying whole-body coordination of ciliary activity in the Platynereis larva

    Csaba Verasztó, Nobuo Ueda ... Gáspár Jékely
    Connectomic reconstruction combined with activity imaging uncovered a rhythmically active neuronal circuit for the coordination of ciliary activity across the whole body of a marine larva.
    1. Neuroscience

    An inhibitory gate for state transition in cortex

    Stefano Zucca, Giulia D’Urso ... Tommaso Fellin
    Two major subtypes of cortical interneurons, the PV and the SST positive cells, causally contribute to the regulation of large-scale state transitions in the cortex.
    1. Cell Biology
    2. Developmental Biology

    Macrophages are necessary for epimorphic regeneration in African spiny mice

    Jennifer Simkin, Thomas R Gawriluk ... Ashley W Seifert
    Inflammatory cells differentially regulate a scarring versus a regenerating response to injury in mammals.
    1. Neuroscience

    Identification of octopaminergic neurons that modulate sleep suppression by male sex drive

    Daniel R Machado, Dinis JS Afonso ... Kyunghee Koh
    The balance between sleep and sex drives determines whether male flies sleep or court, and a subset of octopaminergic neurons interact with the Fruitless-expressing courtship circuit to suppress sleep for sustained courtship.
    1. Microbiology and Infectious Disease

    Plasmodium P36 determines host cell receptor usage during sporozoite invasion

    Giulia Manzoni, Carine Marinach ... Olivier Silvie
    Host CD81 and Scavenger Receptor BI operate independently to mediate invasion of hepatocytes by different species of Plasmodium sporozoites, which use the parasite protein P36 as a key determinant of the entry route.
    1. Neuroscience

    Voltage-gated Na+ currents in human dorsal root ganglion neurons

    Xiulin Zhang, Birgit T Priest ... Michael S Gold
    Human sensory neurons may not only bridge a critical gap between drug discovery and clinical trials, but force a re-evaluation of basic assumptions about the mechanisms controlling primary afferent excitability.
    1. Neuroscience

    Humans treat unreliable filled-in percepts as more real than veridical ones

    Benedikt V Ehinger, Katja Häusser ... Peter König
    In a forced decision between two identical percepts, subjects preferentially rely on inferred internally generated over veridically seen percepts.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Helical jackknives control the gates of the double-pore K+ uptake system KtrAB

    Marina Diskowski, Ahmad Reza Mehdipour ... Inga Hänelt
    The K(+) uptake system KtrAB is controlled by an allosteric mechanism entirely new for membrane channels, which operates the channel gate over a 35 Å distance.
    1. Biochemistry and Chemical Biology

    Evolution of an intricate J-protein network driving protein disaggregation in eukaryotes

    Nadinath B Nillegoda, Antonia Stank ... Bernd Bukau
    The emergence of complementary electrostatic potentials after the prokaryotic-to-eukaryotic split drives physical and functional cooperation between canonical class A and class B J-proteins to boost protein disaggregation.
    1. Neuroscience

    The murine catecholamine methyltransferase mTOMT is essential for mechanotransduction by cochlear hair cells

    Christopher L Cunningham, Zizhen Wu ... Ulrich Müller
    Murine TOMT is essential for transport of mechanotransduction components to stereocilia in cochlear hair cells.
    1. Structural Biology and Molecular Biophysics

    Structural basis of cooperativity in kinesin revealed by 3D reconstruction of a two-head-bound state on microtubules

    Daifei Liu, Xueqi Liu ... Charles V Sindelar
    A novel algorithm is used to solve the first 3D reconstruction of a stepping kinesin dimer on microtubules, directly visualizing the conformational effects of inter-head strain and giving novel insights into the motility mechanism.
    1. Neuroscience

    Catecholaminergic challenge uncovers distinct Pavlovian and instrumental mechanisms of motivated (in)action

    Jennifer C Swart, Monja I Froböse ... Hanneke EM den Ouden
    Motivational coupling of action to reward and inhibition to punishment is subserved by dissociable learning and choice processes, and is modulated by dopamine/noradrenaline transporter blockade.
    1. Cell Biology

    The Sec61 translocon limits IRE1α signaling during the unfolded protein response

    Arunkumar Sundaram, Rachel Plumb ... Malaiyalam Mariappan
    Building on previous work (Plumb et al., 2015), it is shown that the Sec61 translocon controls the oligomerization, activation and inactivation of Ire1α during endoplasmic reticulum stress.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    Mutational phospho-mimicry reveals a regulatory role for the XRCC4 and XLF C-terminal tails in modulating DNA bridging during classical non-homologous end joining

    Davide Normanno, Aurélie Négrel ... Mauro Modesti
    In concert phosphorylation site modification of both XRCC4 and XLF C-terminal disordered tails promotes disassembly of XRCC4/XLF DNA tethers during c-NHEJ.
    1. Cell Biology

    Sphingomyelin metabolism controls the shape and function of the Golgi cisternae

    Felix Campelo, Josse van Galen ... Vivek Malhotra
    Association of curvature generating proteins to the Golgi membranes by sphingomyelin metabolism essentially controls the flatness of a Golgi cisterna that is necessary for efficient sorting and export.
    1. Cell Biology
    2. Neuroscience

    Enhanced FIB-SEM systems for large-volume 3D imaging

    C Shan Xu, Kenneth J Hayworth ... Harald F Hess
    Complete neuronal circuits can be reconstructed, and whole eukaryotic cells imaged, at less than 10 nm isotropic resolution.
    1. Structural Biology and Molecular Biophysics
    2. Neuroscience

    A selectivity filter at the intracellular end of the acid-sensing ion channel pore

    Timothy Lynagh, Emelie Flood ... Stephan A Pless
    Sodium selectivity of acid-sensing ion channels is mediated by negatively charged side chains and not by a size-exclusion mechanism.
    1. Immunology and Inflammation

    Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell help

    Ting-ting Zhang, David G Gonzalez ... Ann M Haberman
    CD40 signaling is necessary to generate the immediate precursors of GC B cells, transition to the BCL6hi follicular state is promoted by a regional and transient diminution of T cell help.
    1. Structural Biology and Molecular Biophysics
    2. Immunology and Inflammation

    Synthekines are surrogate cytokine and growth factor agonists that compel signaling through non-natural receptor dimers

    Ignacio Moraga, Jamie B Spangler ... K Christopher Garcia
    Synthetic cytokines engage new signaling programs with therapeutic potential.
    1. Structural Biology and Molecular Biophysics
    2. Computational and Systems Biology

    Modeling Hsp70/Hsp40 interaction by multi-scale molecular simulations and coevolutionary sequence analysis

    Duccio Malinverni, Alfredo Jost Lopez ... Alessandro Barducci
    Integration of complementary computational approaches reveals an evolutionarily conserved interaction interface between molecular chaperones Hsp70 and Hsp40, rationalizing previous observations.
    1. Cell Biology
    2. Evolutionary Biology

    Chimeric origins of ochrophytes and haptophytes revealed through an ancient plastid proteome

    Richard G Dorrell, Gillian Gile ... Chris Bowler
    An in silico reconstruction of a chloroplast that existed hundreds of millions of years ago casts new insights in the evolutionary processes, endosymbioses and chimerism events that shape the origin of plastids.
    1. Developmental Biology

    Intracellular uptake of macromolecules by brain lymphatic endothelial cells during zebrafish embryonic development

    Max van Lessen, Shannon Shibata-Germanos ... Stefan Schulte-Merker
    The discovery of a unique brain lymphatic cell type in the zebrafish model will facilitate the study of embryonic development and physiology, an essential mission to understand how clearance of macromolecules impact neurological diseases.
    1. Computational and Systems Biology

    Kinetic modeling predicts a stimulatory role for ribosome collisions at elongation stall sites in bacteria

    Michael A Ferrin, Arvind R Subramaniam
    Collision between ribosomes can cause dissociation of stalled ribosomes from messenger RNAs during the process of mRNA translation.
    1. Developmental Biology

    The Hippo pathway effector YAP is an essential regulator of ductal progenitor patterning in the mouse submandibular gland

    Aleksander D Szymaniak, Rongjuan Mi ... Xaralabos Varelas
    The transcriptional regulator YAP directs the specification and differentiation of stem cells that give rise to salivary gland ductal epithelium.
    1. Immunology and Inflammation

    Na+ influx via Orai1 inhibits intracellular ATP-induced mTORC2 signaling to disrupt CD4 T cell gene expression and differentiation

    Yong Miao, Jaya Bhushan ... Monika Vig
    Non-specific sodium entry inhibits T cell receptor induced gene expression and differentiation of T cells by depleting intracellular ATP and disrupting mTORC2 dependent signalling axis.
    1. Ecology

    Digitizing mass spectrometry data to explore the chemical diversity and distribution of marine cyanobacteria and algae

    Tal Luzzatto-Knaan, Neha Garg ... Pieter C Dorrestein
    Mass spectrometry has potential as a tool for ecological studies and bioprospecting of natural products from marine cyanobacteria and algae.
    1. Developmental Biology
    2. Neuroscience

    Analogous mechanism regulating formation of neocortical basal radial glia and cerebellar Bergmann glia

    Xin Heng, Qiuxia Guo ... James YH Li
    Genome-wide transcriptional profiling and genetic analyses reveal conserved mechanisms underlying the generation of neocortical basal radial glia and cerebellar Bergmann glia.
    1. Neuroscience

    Odor identity coding by distributed ensembles of neurons in the mouse olfactory cortex

    Benjamin Roland, Thomas Deneux ... Alexander Fleischmann
    In vivo calcium imaging reveals how odor identity is encoded in the activity of large, distributed ensembles of olfactory cortex neurons in mice.
    1. Developmental Biology
    2. Neuroscience

    USP5/Leon deubiquitinase confines postsynaptic growth by maintaining ubiquitin homeostasis through Ubiquilin

    Chien-Hsiang Wang, Yi-Chun Huang ... Cheng-Ting Chien
    Maintenance of ubiquitin homeostasis is essential for proper control of the size of postsynaptic density and the growth of specialized membrane structure.
    1. Neuroscience

    Noradrenaline blockade specifically enhances metacognitive performance

    Tobias U Hauser, Micah Allen ... Raymond J Dolan
    The neurotransmitter noradrenaline selectively modulates metacognition, the conscious insight into one's performance, but does not alter perceptual decision making, revealing that different neuromodulators affect different stages of a decision making process.
    1. Neuroscience

    Reciprocal synapses between mushroom body and dopamine neurons form a positive feedback loop required for learning

    Isaac Cervantes-Sandoval, Anna Phan ... Ronald L Davis
    Structural and functional analysis of axonal-axonal reciprocal connections between dopamine neurons and Kenyon cells provides insight into the brain computations for normal associative olfactory learning.
    1. Evolutionary Biology

    Homo naledi and Pleistocene hominin evolution in subequatorial Africa

    Lee R Berger, John Hawks ... Eric M Roberts
    A late Middle Pleistocene age for Homo naledi demonstrates a diversity of hominin species in Africa at this critical time in the archaeological record.
    1. Chromosomes and Gene Expression

    Super-resolution imaging of a 2.5 kb non-repetitive DNA in situ in the nuclear genome using molecular beacon probes

    Yanxiang Ni, Bo Cao ... Hanben Niu
    Molecular beacon based FISH shows the capability of visualizing a 2.5 kb non-repetitive genomic DNA sequence in situ in human or mouse nuclear genome at super resolution.
    1. Evolutionary Biology

    New fossil remains of Homo naledi from the Lesedi Chamber, South Africa

    John Hawks, Marina Elliott ... Lee R Berger
    The discovery of new skeletal remains of Homo naledi in the Lesedi Chamber, South Africa, adds more evidence to our understanding of the morphology and behavior of this recently discovered species.
    1. Neuroscience

    MCTP is an ER-resident calcium sensor that stabilizes synaptic transmission and homeostatic plasticity

    Özgür Genç, Dion K Dickman ... Graeme W Davis
    MCTP is a novel presynaptic calcium sensor, resident within the endoplasmic reticulum, that is required for normal baseline neurotransmission, short-term synaptic plasticity and presynaptic homeostatic plasticity.
    1. Evolutionary Biology

    The age of Homo naledi and associated sediments in the Rising Star Cave, South Africa

    Paul HGM Dirks, Eric M Roberts ... Lee R Berger
    Independent dating techniques have established that the H. naledi fossils are between 236 and 335 thousand years old, indicating that small-brained hominins with relatively primitive body shapes co-existed with our early ancestors in Africa.
    1. Medicine
    2. Microbiology and Infectious Disease

    Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa

    Elin Näsström, Christopher M Parry ... Stephen Baker
    Mass spectrometry on plasma from patients with typhoid fever and other febrile disease identified and validated 24 metabolites that can distinguish typhoid from other febrile diseases, providing a new approach for typhoid diagnostics.
    1. Evolutionary Biology
    2. Microbiology and Infectious Disease

    Evolution of reduced co-activator dependence led to target expansion of a starvation response pathway

    Bin Z He, Xu Zhou, Erin K O’Shea
    The phosphate starvation response network in a commensal yeast evolved to expand its downstream targets via changes in the main transcription factor's dependence on its co-activator, potentially altering the physiological response.
    1. Cell Biology
    2. Computational and Systems Biology

    Functional mapping of yeast genomes by saturated transposition

    Agnès H Michel, Riko Hatakeyama ... Benoît Kornmann
    A new method maps functional and structural features of yeast genomes with unprecedented ease and throughput, which allows identification of protein domains at the genome scale.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    Multiple short windows of calcium-dependent protein kinase 4 activity coordinate distinct cell cycle events during Plasmodium gametogenesis

    Hanwei Fang, Natacha Klages ... Mathieu Brochet
    CDPK4 is a pleiotropic regulator controlling initiation of DNA replication, mitotic spindle assembly and flagellar activation during the early stages of Plasmodium transmission.
    1. Neuroscience

    Learning multiple variable-speed sequences in striatum via cortical tutoring

    James M Murray, G Sean Escola
    Inspired by the sparse, sequential neural activity patterns observed in striatum, a new circuit model implements variable-speed activity, the encoding of multiple sequences, and a tutor/student relationship between cortex and striatum.
    1. Ecology
    2. Microbiology and Infectious Disease

    A diverse host thrombospondin-type-1 repeat protein repertoire promotes symbiont colonization during establishment of cnidarian-dinoflagellate symbiosis

    Emilie-Fleur Neubauer, Angela Z Poole ... Virginia M Weis
    The colonization of corals and their relatives by intracellular microalgae is facilitated by immunity proteins in the animal that contain thrombospondin-type-1 repeats, elucidating the inter-partner recognition processes required for the establishment of this ecologically important symbiosis.
    1. Structural Biology and Molecular Biophysics
    2. Neuroscience

    Autoinhibition of Munc18-1 modulates synaptobrevin binding and helps to enable Munc13-dependent regulation of membrane fusion

    Ewa Sitarska, Junjie Xu ... Josep Rizo
    Biophysical and functional data strongly support the notion that Munc18-1 acts as a template to assemble the neuronal SNARE complex, and that inhibition of this activity underlies diverse forms of regulation of neurotransmitter release.
    1. Cell Biology

    Metaphase chromosome structure is dynamically maintained by condensin I-directed DNA (de)catenation

    Ewa Piskadlo, Alexandra Tavares, Raquel A Oliveira
    Condensin I maintains chromosome organization throughout metaphase by preventing erroneous topoisomerase II-dependent sister chromatid re-entanglements.
    1. Neuroscience

    Shank is a dose-dependent regulator of Cav1 calcium current and CREB target expression

    Edward Pym, Nikhil Sasidharan ... Joshua M Kaplan
    Changes in Shank gene dosage alter voltage-activated calcium current and calcium-activated gene expression in a manner that parallels the effects of human Shank copy number variation on psychiatric disease risk.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Resolving stem and progenitor cells in the adult mouse incisor through gene co-expression analysis

    Kerstin Seidel, Pauline Marangoni ... Ophir D Klein
    Gene co-expression analysis identifies coherent transcriptional patterns driven by distinct cell types in the mouse incisor, and functional studies of candidate genes reveal how the tissues are maintained through stem cell-fueled renewal.
    1. Biochemistry and Chemical Biology

    SENP8 limits aberrant neddylation of NEDD8 pathway components to promote cullin-RING ubiquitin ligase function

    Kate E Coleman, Miklós Békés ... Tony T Huang
    Aberrant neddylation of non-cullin substrates disrupts normal cell cycle progression.
    1. Ecology
    2. Physics of Living Systems

    Microbial consortia at steady supply

    Thibaud Taillefumier, Anna Posfai ... Ned S Wingreen
    In a consumer-resource model obeying the physical requirement of flux conservation, metabolic competition between microbes yields consortia of cell types that collectively resist invasion via optimal use of resources.
    1. Neuroscience

    Peroxisomal dysfunctions cause lysosomal storage and axonal Kv1 channel redistribution in peripheral neuropathy

    Sandra Kleinecke, Sarah Richert ... Celia Michèle Kassmann
    Dysfunctions of myelin peroxisomes cause a lysosomal storage-like disorder associated with alterations in glial and axonal membranes, which is the likely cause of nerve impairment in peroxisomal disorders.
    1. Neuroscience

    Beta band oscillations in motor cortex reflect neural population signals that delay movement onset

    Preeya Khanna, Jose M Carmena
    Using a sequential neurofeedback-arm reaching task, a new link is established among population neural activity patterns, generation of beta oscillations, and motor behavior changes.
    1. Cancer Biology
    2. Cell Biology

    TCF7L1 promotes skin tumorigenesis independently of β-catenin through induction of LCN2

    Amy T Ku, Timothy M Shaver ... Hoang Nguyen
    Overexpression of TCF7L1 overrides oncogenic Ras-induced senescence, induces cell migration, and promotes growth of skin squamous cell carcinoma independently of its interaction with β-catenin.
    1. Cancer Biology
    2. Cell Biology

    Regulation of localization and function of the transcriptional co-activator YAP by angiomotin

    Susana Moleirinho, Sany Hoxha ... Joseph L Kissil
    Phosphorylation of Angiomotin regulates YAP localization and activity.
    1. Structural Biology and Molecular Biophysics
    2. Cell Biology

    Single-protein detection in crowded molecular environments in cryo-EM images

    J Peter Rickgauer, Nikolaus Grigorieff, Winfried Denk
    High-resolution template matching makes small, densely embedded proteins detectable.
    1. Structural Biology and Molecular Biophysics
    2. Chromosomes and Gene Expression

    CTCF and cohesin regulate chromatin loop stability with distinct dynamics

    Anders S Hansen, Iryna Pustova ... Xavier Darzacq
    Single-molecule imaging of CTCF and cohesin in live cells suggests that chromatin loops are dynamic structures that frequently form and fall apart.
    1. Genetics and Genomics

    Introduction of a male-harming mitochondrial haplotype via ‘Trojan Females’ achieves population suppression in fruit flies

    Jonci Nikolai Wolff, Neil J Gemmell ... Damian K Dowling
    Mitochondrial genomes harbor male-fertility-reducing mutations that can be harnessed to control population viability as a novel approach to control economic and environmental pests.
    1. Cell Biology
    2. Neuroscience

    A novel ALS-associated variant in UBQLN4 regulates motor axon morphogenesis

    Brittany M Edens, Jianhua Yan ... Yongchao C Ma
    A novel ALS-associated variant in UBQLN4 impairs proteasome function and beta-catenin degradation to drive aberrant axon morphogenesis in motor neurons.
    1. Biochemistry and Chemical Biology
    2. Plant Biology

    RISC-interacting clearing 3’- 5’ exoribonucleases (RICEs) degrade uridylated cleavage fragments to maintain functional RISC in Arabidopsis thaliana

    Zhonghui Zhang, Fuqu Hu ... Xiuren Zhang
    AGO protein-interacting exoribonucleases clear RNA induced silencing complex (RISC)-resulting 5' cleavage products in time to recycle RISC and miRNAs.
    1. Cell Biology

    Protein Phosphatase 1 inactivates Mps1 to ensure efficient Spindle Assembly Checkpoint silencing

    Margarida Moura, Mariana Osswald ... Carlos Conde
    Inactivation of the master mitotic checkpoint regulator Mps1 by protein phosphatase 1 is required for timely segregation of the genetic material during cell division.
    1. Computational and Systems Biology
    2. Neuroscience

    Saccadic suppression as a perceptual consequence of efficient sensorimotor estimation

    Frédéric Crevecoeur, Konrad P Kording
    Neural computations necessary for efficient control of saccades capture the phenomenon of saccadic suppression, which suggests that neural resources are shared for perception and control.
    1. Cell Biology

    Nuclear export of misfolded SOD1 mediated by a normally buried NES-like sequence reduces proteotoxicity in the nucleus

    Yongwang Zhong, Jiou Wang ... Shengyun Fang
    Cellular and genetic approaches reveal that exposure of a normally buried nuclear export signal (NES)-like sequence mediates export of ALS-linked mutant and misfolded wild-type SOD1 to the cytoplasm by CRM1.
    1. Chromosomes and Gene Expression

    Synthetically modified guide RNA and donor DNA are a versatile platform for CRISPR-Cas9 engineering

    Kunwoo Lee, Vanessa A Mackley ... Niren Murthy
    The guide RNA and donor DNA of the CRISPR/Cas system tolerate large chemical modifications and can be engineered for enhanced delivery and gene editing.
    1. Microbiology and Infectious Disease

    Adaptive tuning of mutation rates allows fast response to lethal stress in Escherichia coli

    Toon Swings, Bram Van den Bergh ... Jan Michiels
    Population mutation rates are highly flexible and evolvable under extreme stress conditions, matching changes in selective pressure to avoid extinction of the entire population.
    1. Cell Biology
    2. Developmental Biology

    The Sec14-like phosphatidylinositol transfer proteins Sec14l3/SEC14L2 act as GTPase proteins to mediate Wnt/Ca2+ signaling

    Bo Gong, Weimin Shen ... Shunji Jia
    Sec14l3/SEC14L2 respond to upstream Wnt/Frizzled/Dvl stimulation to recruit and activate phospholipase Cδ4a (Plcδ4a) to further initiate calcium release.
    1. Neuroscience

    The role of PDF neurons in setting the preferred temperature before dawn in Drosophila

    Xin Tang, Sanne Roessingh ... Fumika N Hamada
    In Drosophila, key neurons controlling sleep play an important role in adjusting the temperature set-point before dawn via time-dependent neuronal plasticity within the clock circuits.
    1. Developmental Biology

    Loss of Ptpn11 (Shp2) drives satellite cells into quiescence

    Joscha Griger, Robin Schneider ... Carmen Birchmeier
    The stem cells of the postnatal muscle allow postnatal muscle growth and repair and withdraw from the cell cycle when the tyrosine phosphatase Ptpn11 (Shp2) is inhibited or mutated in mice.
    1. Cell Biology

    PDE2A2 regulates mitochondria morphology and apoptotic cell death via local modulation of cAMP/PKA signalling

    Stefania Monterisi, Miguel J Lobo ... Manuela Zaccolo
    The enzyme phosphodiesterase 2A2 localises at the mitochondrial membrane and its inhibition results in a local increase in cAMP concentration, mitochondrial elongation and resistance to apoptosis.
    1. Neuroscience

    Decreased microRNA levels lead to deleterious increases in neuronal M2 muscarinic receptors in Spinal Muscular Atrophy models

    Patrick J O'Hern, Inês do Carmo G. Gonçalves ... Anne C Hart
    In invertebrate and vertebrate models of Spinal Muscular Atrophy, diminished SMN protein causes Gemin3-dependent decreases in microRNA function, leading to upregulated M2 muscarinic receptor and deleterious consequences.
    1. Biochemistry and Chemical Biology

    Control of lipid domain organization by a biomimetic contractile actomyosin cortex

    Sven Kenjiro Vogel, Ferdinand Greiss ... Petra Schwille
    Building on previous work (Vogel et al., 2013b), it is shown that myosin-driven actin filament rearrangements actively move, split or fuse individual lipid domains and change their overall shape.
    1. Ecology

    Transcriptome analysis illuminates the nature of the intracellular interaction in a vertebrate-algal symbiosis

    John A Burns, Huanjia Zhang ... Ryan Kerney
    The endosymbiosis between an alga and the spotted salamander shows several parallels to invertebrate-algal symbioses as well as to pathogen associations in vertebrate animals.

Magazine

    1. Neuroscience

    Thermoregulation: How a brain keeps its cool

    Swathi Yadlapalli, Orie T Shafer
    1. Neuroscience

    Axons: The cost of communication in the brain

    Brian A MacVicar, Leigh Wicki-Stordeur, Louis-Philippe Bernier
    1. Neuroscience

    Chemoreception: Keeping carbon dioxide in check

    Alfredo J Garcia III, Jan-Marino Ramirez
    1. Ecology

    Endosymbiosis: Gasping for air

    Steven G Ball, Ugo Cenci